Studies on aorta during development II. Differences in ontogeny of the key enzymes involved in cholesteryl ester synthesis and hydrolysis in rabbit aorta

It is well known that cholesteryl ester accumulation is dramatically increased in the atherosclerotic artery. The enzymes acyl-CoA : cholesterol acyltransferase (ACAT), acid cholesteryl esterase (ACE) and neutral cholesteryl esterase (NCE) may play key roles in the accumulation of cholesteryl esters in the arterial wall. However, very little is known regarding the developmental pattern of the key enzymes involved in cholesteryl ester synthesis and hydrolysis. The total activities of ACAT, ACE and NCE were measured by radioassay using liposorinal substrates in rabbit aortic homogenates. Our results indicate that ACAT activity decreases as a quadratic function with age ( P < 0.05). ACAT activity (pmol/100 mg protein/min) decreased from a high value in the fetus at term (63.3 ± 7.4) to gradually lower values with increasing age. On the other hand, ACE activity (pmol/mg protein/min) was low in the fetus at term, and changed as a quadratic function with age ( P < 0.05) increasing gradually to higher activities with age up to a maximum at 12 weeks then decreased at 21 weeks. NCE activity (pmol/mg protein/min) increased dramatically from a low value in the fetus at term (3.34 ± 0.48) to a maximum value at 1.5 weeks (14.65 ± 2.73) then decreased as a linear function with increasing age up to 21 weeks ( P < 0.05). Plasma total cholesterol (mg/dl) also increased sharply from the fetal value at term of 98.5 ± 5.2 to a maximum value at 1.5 weeks of 666.4 ± 33.4, then decreased as a quadratic function with increasing age up to 21 weeks (40.8 ± 6.7) ( P < 0.05). The free cholesterol content (μg/mg protein) of the aortic tissue was initially high in the fetus (24.8 ±95.9) then increased with age. Examination of the ratio of synthesis to hydrolysis of cholesteryl esters as an index of enzyme activity units demonstrated a very high index in the fetus of 6.1 that rapidly decreased with increasing age in the young adult rabbit down to a value of 0.4 by 21 weeks of age. Correlation coefficients between enzyme activities, plasma cholesterol levels and aortic cholesterol levels indicated (a) a positive correlation of NCE activity with plasma cholesterol, (b) a negative correlation of NCE and ACE with aortic-cholesteryl ester content, and (c) no significant correlation of ACAT activity with either plasma cholesterol or aortic cholesterol content, indicating other factors are involved. These studies show (a) differences in the development pattern of ACAT and cholesteryl esterases